PT  - JOURNAL ARTICLE
AU  - Alsiö, Johan
AU  - Nordenankar, Karin
AU  - Arvidsson, Emma
AU  - Birgner, Carolina
AU  - Mahmoudi, Souha
AU  - Halbout, Briac
AU  - Smith, Casey
AU  - Fortin, Guillaume M.
AU  - Olson, Lars
AU  - Descarries, Laurent
AU  - Trudeau, Louis-Éric
AU  - Kullander, Klas
AU  - Lévesque, Daniel
AU  - Wallén-Mackenzie, Åsa
TI  - Enhanced Sucrose and Cocaine Self-Administration and Cue-Induced Drug Seeking after Loss of VGLUT2 in Midbrain Dopamine Neurons in Mice
AID  - 10.1523/JNEUROSCI.2397-11.2011
DP  - 2011 Aug 31
TA  - The Journal of Neuroscience
PG  - 12593--12603
VI  - 31
IP  - 35
4099  - http://www.jneurosci.org/content/31/35/12593.short
4100  - http://www.jneurosci.org/content/31/35/12593.full
SO  - J. Neurosci.2011 Aug 31; 31
AB  - The mesostriatal dopamine (DA) system contributes to several aspects of responses to rewarding substances and is implicated in conditions such as drug addiction and eating disorders. A subset of DA neurons has been shown to express the type 2 Vesicular glutamate transporter (Vglut2) and may therefore corelease glutamate. In the present study, we analyzed mice with a conditional deletion of Vglut2 in DA neurons (Vglut2f/f;DAT-Cre) to address the functional significance of the glutamate–DA cophenotype for responses to cocaine and food reinforcement. Biochemical parameters of striatal DA function were also examined by using DA receptor autoradiography, immediate-early gene quantitative in situ hybridization after cocaine challenge, and DA-selective in vivo chronoamperometry. Mice in which Vglut2 expression had been abrogated in DA neurons displayed enhanced operant self-administration of both high-sucrose food and intravenous cocaine. Furthermore, cocaine seeking maintained by drug-paired cues was increased by 76%, showing that reward-dependent plasticity is perturbed in these mice. In addition, several lines of evidence suggest that adaptive changes occurred in both the ventral and dorsal striatum in the absence of VGLUT2: DA receptor binding was increased, and basal mRNA levels of the DA-induced early genes Nur77 and c-fos were elevated as after cocaine induction. Furthermore, in vivo challenge of the DA system by potassium-evoked depolarization revealed less DA release in both striatal areas. This study demonstrates that absence of VGLUT2 in DA neurons leads to perturbations of reward consumption as well as reward-associated memory, features of particular relevance for addictive-like behavior.